PROPOSAL (Adapted from the applicant's abstract): Highly active antiretroviral therapy (HAART) results in decreased morbidity and improved survival for individuals with human immunodeficiency virus (HIV) infection. Improved outcomes were first observed with multi-drug regimens containing protease inhibitors (PIs), and are related to durable suppression of viremia with subsequent immune restoration. Evidence suggests that PI use could lead to lipodystrophy, a syndrome including diabetes, disfiguring body habitus changes, and disorders of lipid metabolism. It is unclear whether HIV infection itself, genetics, PIs, or immune system reconstitution may contribute to the development of lipodystrophy. PI-sparing regimens have been developed that efficiently inhibit viral replication. While virologic outcomes appear equivalent, it is unknown whether these newer regimens will lead to a similar degree of immune reconstitution as that seen with PI- containing regimens. This proposal will exploit the design of a funded project entitled: "Mechanisms of Lipodystrophy in HIV-Infected Patients," to address these questions in a randomized, controlled, prospective trial involving 80 human subjects. The investigators hypothesize that PI-sparing and PI-containing regimens lead to similar immune restoration. To test this hypothesis, the primary objective of this study is to characterize and compare measurements of immune reconstitution in HIV-1 infected, antiretroviral naive subjects treated with PI-based versus PI-sparing HAART. The three aims are: 1) to compare cytomegalovirus and HIV-specific CD4+ and CD8+ cell responses over time; 2) to assess the thymic generation of new naive T-cells in patients receiving these two therapeutic regimens; and 3) to qualitatively compare the turnover and restoration of T-cell function in the two groups. Immune reconstitution will be correlated with clinical outcomes such as development of lipodystrophy. Confirmation of the proposed hypothesis will indicate that PI-sparing regimens offer equal efficacy, and fewer complications, than PI-containing regimens.